Get access

Antiglucocorticoid treatments for mood disorders

  • Review
  • Intervention

Authors


Abstract

Background

Antiglucocorticoids may have antidepressant effects and have been reported to be efficacious in the treatment of severe psychiatric disorders. The efficacy and safety of antiglucocorticoid treatments for mood disorders is the subject of this systematic review.

Objectives

To compare the efficacy and safety of antiglucocorticoid agents in the treatment of mood episodes (manic, mixed affective or depressive) with placebo or alternative drug treatment in mood disorders.

Search methods

CCDANCTR-Studies and CCDANCTR-References were searched on 11-9-2007. Additional searches of electronic databases were conducted in December 2006. Conference proceedings were searched. Experts and pharmaceutical companies were contacted.

Selection criteria

Randomised controlled trials comparing antiglucocorticoid drugs in the treatment of mood episodes with placebo or alternative drug treatment in mood disorders were selected.

Data collection and analysis

Data were extracted and the methodological quality of each study was assessed independently by two review authors. Meta-analyses were performed using Review Manager software. Relative risk (RR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes. For continuous data, weighted mean differences (WMD) were calculated.

Main results

Nine studies met criteria for inclusion. A number of drugs were examined, including mifepristone [RU-486], ketoconazole, metyrapone and DHEA. Three trials were in patients with psychotic major depression (pMDD), five trials in non-psychotic major depression and one trial in bipolar disorder. When examining all trials together across all affective episodes, there was no significant difference in the overall proportion of patients responding to antiglucocorticoid treatment over placebo, although the mean change in HAM-D scores indicated a significant difference in favour of treatment (WMD -4.54, 95%CI -6.78 to -2.29). Of the five trials in non-psychotic depression (unipolar or bipolar), there was a significant difference favouring treatment (HAM-D 50% reduction: RR 0.72, 95%CI 0.56 to 0.91). In pMDD, there was no evidence of an overall antidepressant effect (HAM-D 50% reduction: RR 0.98, 95%CI 0.79 to 1.22) or an effect on overall psychopathology (BPRS 30% reduction: RR 0.96, 95%CI 0.76 to 1.22). In these subtypes, the mean change in HAM-D indicated a significant difference in favour of treatment.

Authors' conclusions

The use of antiglucocorticoids in the treatment of mood disorders is at the proof-of-concept stage. Considerable methodological differences exist between studies with respect to the compounds used and the patient cohorts studied. Results in some diagnostic subtypes are promising and warrant further investigation to establish the clinical utility of these drugs in the treatment of mood disorders.

摘要

背景

情感性疾患的抗糖皮質固醇治療

抗糖皮質固醇也許有抗憂鬱的作用,並且對於嚴重精神疾患已有報告指出其有效性。使用抗糖皮質固醇治療情感性疾患的療效及安全性是這個系統性回顧的主題。

目標

比較抗糖皮質固醇製劑與安慰劑或其他藥物在治療情感發作(躁症、混和發作、或鬱症)的療效及安全性。

搜尋策略

在11 – 9 – 2007搜尋CCDANCTRStudies and CCDANCTRReferences的資料。2006年12月額外進行電子資料的搜尋。搜尋研討會手冊,並徵詢了專家及藥商公司的意見。

選擇標準

選擇比較抗糖皮質固醇製劑與安慰劑或其他藥物在治療情感發作的隨機對照試驗

資料收集與分析

兩位審查者獨立地擷取資料並且對每個研究評估其使用方法的品質. 使用回顧管理軟體(Review Manager software)來執行Metaanalyses. 對於二分變項結果會去計算Relative risk (RR) 及 95% confidence intervals (CI). 至於連續性的資料,則會計算weighted mean differences (WMD).

主要結論

有九個試驗符合納入標準. 其中檢視了幾種藥物,包括[RU486], ketoconazole, metyrapone 以及 DHEA.三個試驗的受試者是伴有精神症狀的重度憂鬱症患者(pMDD),五個試驗是單純的重度憂鬱症,而一個試驗是雙極性疾患. 當一同檢視所有試驗的所有情緒發作後發現,對於抗糖皮質固醇治療有反應的整體比率與對照組相比,並沒有明顯的不同,雖然HAMD scores 的平均分數的改變顯示出治療組有顯著的差異((HAMD 50% reduction: RR 0.72, 95%CI 0.56 to 0.91). 在五個單純重度憂鬱症的試驗中(單極性或雙極性),藥物治療的有效性呈現顯著的差異(HAMD 50% reduction: RR 0.72, 95%CI 0.56 to 0.91). 而在pMDD的試驗中,並沒有證據顯示出此藥具有整體抗憂鬱的效果(HAMD 50% reduction: RR 0.98, 95%CI 0.79 to 1.22)或是對於整體精神病理方面的改善有所幫助(BPRS 30% reduction: RR 0.96, 95%CI 0.76 to 1.22). 不過在這些亞型中,對於HAMD平均值的改變都顯示出明顯差異(意即抗糖皮質固醇治療較有效).

作者結論

使用抗糖皮質固醇治療情感性疾患仍舊處於概念驗證階段. 在各個研究間,不論是在藥物上或者是在所研究的患者世代上, 其使用的方法還是存在相當大的差異. 在一些亞型中,雖然呈現出確定的療效,但還是需要更進一步的研究來確定這種藥物在治療情感性疾患上其臨床使用的正當性.

翻譯人

本摘要由彰化基督教醫院廖慈凰翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

情感性疾患的抗糖皮質固醇治療 許多情感性疾患的患者除了情緒方面的症狀外還伴隨有記憶力及專注力不佳的問題. 有證據指出這跟壓力系統中所謂的下視丘-腦下垂體-腎上腺皮質體徑(HPA)過度活化有關. 因為這將導致壓力賀爾蒙可體松(cortisol)的過量分泌. 因此,針對這個壓力路徑產生作用的藥物可能會有療效. 本次回顧的目的就是要去瞭解使用抗糖皮質固醇治療情感性疾患的效果及安全性. 有九個符合納入標準的試驗. 這當中檢視了許多藥物,包括[RU486] (n = 4), ketoconazole (n = 2), metyrapone (n = 2), 以及DHEA (n = 1). 有三個試驗的受試者是伴有精神症狀的重度憂鬱症患者(pMDD),五個試驗是單純的重度憂鬱症,而一個試驗是雙極性疾患(目前處於憂鬱狀態,未伴隨有精神症狀). 當一同檢視所有試驗的所有情感發作後發現,對於抗糖皮質固醇治療有反應(HAMD 減少50%分數)的整體比率與對照組相比,並沒有明顯的不同,然而, HAMD scores 的平均分數的改變上(WMD; baseline to endpoint)卻顯示出治療組有顯著的差異. 另外,在特定的亞型上,的確清楚地呈現出此藥的有效性. 在五個未伴隨精神症狀的憂鬱患者試驗中(單極性或雙極性),藥物治療的有效性呈現顯著差異,而在伴隨精神症狀的憂鬱患者試驗中,並沒有在抗憂鬱或是整體的精神病理上面顯示出療效(BPRS 30% reduction). 不過量表分數的weighted mean differences (WMD)在這些亞型中卻呈現出顯著的差異,顯示治療有效. 目前為止,只有一個試驗檢視抗糖皮質固醇在神經心理功能上面的影響. 而副作用的報告並不多;整個來說,只有出現紅疹抗糖皮質固醇達到顯著差異而且在兩個研究中被報告. 總結而言,使用抗糖皮質固醇治療情感性疾患以及精神疾患確實仍舊處於概念驗證階段. 彼此研究間關於使用的藥物,研究的患者世代以及方法學上仍存在相當大的差異. 有一些診斷亞型呈現出可能的療效,不過仍需要更進一步的研究來驗證這類藥物臨床應用的有效性.

Plain language summary

Antiglucocorticoid treatments for mood disorders

Many patients with mood disorders report problems with memory and concentration, alongside their mood symptoms. There is some evidence that a possible cause of these problems is an overactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the body's natural stress system. This leads to an overproduction of the stress-hormone, cortisol. Therefore, it is possible that drugs which target the HPA axis may be of benefit. The efficacy and safety of antiglucocorticoids in the treatment of mood disorders was the subject of this systematic review. Nine studies met criteria for inclusion. Of these, a number of drugs were examined, including: mifepristone [RU-486] (n=4), ketoconazole (n=2), metyrapone (n=2), and DHEA (n=1). Three of the trials were in patients with psychotic major depression (pMDD), five trials in non-psychotic major depression and one trial in patients with bipolar disorder (currently depressed; non-psychotic). Overall, when examining all trials together over all affective episodes, there was no significant difference in the overall proportion of patients responding (HAM-D 50% reduction) to treatment with antiglucocorticoids over placebo. However the mean change (WMD; baseline to end-point) in HAM-D scores indicated a significant difference in favour of treatment . There is clearer evidence of efficacy in specific diagnostic subtypes. Of the five trials in non-psychotic depression (unipolar or bipolar), there was a significant difference in favour of treatment. In psychotic depression, there was no evidence of an overall antidepressant effect or an effect on overall psychopathology (BPRS 30% reduction). In these subtypes the mean change (WMD) in scores indicated a significant difference in favour of treatment . To date only one trial has examined the impact of antiglucocorticoids on neuropsychological functioning. There are limited reports on side effects; overall, the only event to reach significance was the incidence of a rash occurring more often after active treatment, and this was reported in two studies . In summary, the use of antiglucocorticoids in the treatment of mood disorders and psychosis is very much at the proof-of-concept stage. A great deal of difference exists between studies with respect to the compounds used, patient cohort under investigation and methodology. Results in some diagnostic subtypes are promising and warrant further examination to better examine the clinical utility of this class of drug.

Get access to the full text of this article

Ancillary